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Biosynthesis of 3-Amino-5-hydroxybenzoic Acid, the Precursor of mC 7 N Units in Ansamycin Antibiotics

1996; American Chemical Society; Volume: 118; Issue: 32 Linguagem: Inglês

10.1021/ja9601292

1943-2984

Chun-Gyu Kim, Andreas Kirschning, Phillipe Bergon, Pei Zhou, Esther Su, Bernd Sauerbrei, Sandra Ning, Yonghyun Ahn, Michael Breuer, Eckhard Leistner, Heinz G. Floss,

Synthetic Organic Chemistry Methods

The biosynthetic pathway of 3-amino-5-hydroxybenzoic acid (AHBA) formation was studied with cell-free extracts from the rifamycin B producer, Amycolatopsis mediterranei S699, and the ansatrienin A producer, Streptomyces collinus Tü1892. Phosphoenolpyruvate (PEP) plus erythrose 4-phosphate (E4P) gave AHBA in low but nevertheless significant (6%) yield. 3,4-Dideoxy-4-amino-d-arabino-heptulosonic acid 7-phosphate (aminoDAHP) was converted efficiently into AHBA (45%), as were 5-deoxy-5-amino-3-dehydroquinic acid (aminoDHQ, 41%) and 5-deoxy-5-amino-3-dehydroshikimic acid (aminoDHS, 95%). On the other hand, the normal shikimate pathway intermediate, 3-deoxy-d-arabino-heptulosonic acid 7-phosphate (DAHP) did not give rise to AHBA under these conditions. AminoDAHP (9%) was produced by incubation of [14C]PEP and E4P, but not of [14C]DAHP, with the cell-free extracts. The results demonstrate the operation of a new variant of the shikimate pathway in the formation of the mC7N units of ansamycin, and presumably also mitomycin, antibiotics which leads from PEP, E4P, and a nitrogen source directly to aminoDAHP and then via aminoDHQ and aminoDHS to AHBA.